Prospective studies on Parkinson's disease

帕金森病的前瞻性研究

• 批准号: 7594019
• 负责人: HONGLEI CHEN
• 金额: $ 33.61万
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7594019
• 关键词: Address; Affect; Age; American; American Cancer Society; Aspirin; Baseline Surveys; Case-Control Studies; Chronic Disease; Clinical Course of Disease; Collaborations; Collection; Communicable Diseases; Computer Assisted; Condition; Consumption; DNA; Data Collection; Diagnostic; Diet; Dietary Factors; Disease; Elderly; Environment; Environmental Risk Factor; Epidemiologic Studies; Etiology; Exposure to; Follow-Up Studies; Future; Gender; Genes; Genetic; Goals; Health; Health Professional; Heavy Metals; Incidence; Infection; Inflammation; Investigation; Life Style; Link; Longitudinal Studies; Nerve Degeneration; Neurodegenerative Disorders; Non-Steroidal Anti-Inflammatory Agents; Nurses' Health Study; Occupational; Parkinson Disease; Pathogenesis; Patients; Pesticides; Pharmaceutical Preparations; Phase; Population; Prevention; Prospective Studies; Psyche structure; Public Health Schools; Recording of previous events; Reporting; Research; Research Infrastructure; Research Project Grants; Risk; Risk Factors; Role; Staging; Surveys; Symptoms; Telephone Interviews; Time; Woman; Work; anticancer research; base; cancer prevention; case control; cohort; design; disability; disorder risk; early onset; follow-up; gene environment interaction; genetic risk factor; interest; men; nutrition; prospective

Parkinsons disease (PD) is the second most prevalent neurodegenerative disease in the elderly population and its causes are largely unknown. Although several genes have been identified to be responsible for some of the early onset familial cases, the causes of most PD cases remained unexplained. Epidemiological studies on PD environmental risk factors are proved difficult, due to the low incidence, the insidious onset and the clinical course of the disease. In collaboration with Dr. Alberto Ascherios group at Harvard School of Public Health, I have been investigating dietary and lifestyle risk factors in relation to PD risk in three well established prospective cohorts: the Health Professionals Follow-up Study, the Nurses Health Study, and the Cancer Prevention Study II Nutrition Cohort from American Cancer Society. The prospective design is important in PD epidemiological research as it avoids many of the potential biases that the previous case-control studies had. Further, these three cohrots are to date the largest prospective studies on PD and have generated some interesting results that need to be validated in future investigations. Consistent findings from these studies included a positive association between dairy consumption and risk of PD and an inverse association between non-aspirin NSAIDs use and PD risk. Recently, we were also able to provide to date the strongest prospective evidence linking pesticide use and a higher PD risk. Further, I am also developing a new research project on PD (the Parkinsons Genes and Environment Study (PAGE)) to investigate environmental and genetic risk factors for PD in the NIH-AARP Diet and Health Study, which is a large prospective cohort that was initiated in mid-1990s by Dr. Arthur Schatzkin at NCI for cancer research. Over half a million US men and women 50 years or older participated in the baseline surveys in 1995 and 1996 and a follow-up survey is now underway to document the occurrence of chronic diseases, including PD. Therefore, this cohort provides an excellent infrastructure for PD research. The PAGE study includes two phases: PAGE 1 is a longitudinal study to investigate whether diet/lifestyle are related to PD risk, using exposure information collected at baseline and PD cases identified in the follow-up. PAGE 2 will be a case-control study to examine other environmental/occupational risk factors in relation to PD and will require further retrospective exposure data collection from both cases and selected controls. For both projects, the key is to do an accurate diagnostic confirmation of PD cases, and an intrinsic component of both projects is DNA collection, which will allow us to conduct case-control analyses of diet-gene / environment-gene interactions. Therefore, PD diagnostic confirmation and DNA collection will be carried out as part of PAGE 1. In PAGE2, we will conduct retrospective data collection using computer assisted telephone interview (CATI). Of particular interest are exposures to pesticides, heavy metals, medication, and history of infectious diseases. Eventually, we expect to confirm approximately 1,000 incident PD cases (1996-2004) based on the age- and gender-specific incidence from other large prospective cohorts with similar design. This will make the study the largest longitudinal study on PD to date and thus contribute significantly to our understanding of the environmental and genetic causes of late onset sporadic PD. We started data collection for PAGE I project this year and plan to finish it later next year. During the same time, we plan to launch the PAGE II project. In addition to these projects, I am also working on a few smaller projects on PD and related neurodegenerative conditions.

帕金森氏病（PD）是老年人群中第二大流行的神经退行性疾病，其原因在很大程度上是未知的。尽管已经确定有几个基因是对一些早期家庭病例的原因，但大多数PD病例的原因仍无法解释。由于发病率低，阴险发作和疾病的临床过程，证明对PD环境风险因素的流行病学研究被证明是困难的。 与哈佛大学公共卫生学院的Alberto Ascherios集团合作，我一直在调查三个良好成熟的前瞻性人群中与PD风险有关的饮食和生活方式危险因素：卫生专业人员随访研究，护士健康研究和癌症预防研究II美国癌症学会II营养队列。前瞻性设计在PD流行病学研究中很重要，因为它避免了先前病例对照研究的许多潜在偏见。此外，这三个同胞是对PD的最大前瞻性研究，并产生了一些有趣的结果，这些结果需要在未来的研究中得到验证。这些研究的一致发现包括乳制品消费和PD风险之间的正相关，以及非阿斯皮蛋白NSAIDS使用与PD风险之间的反相关性。最近，我们还能够提供迄今为止，将农药使用和更高的PD风险联系起来的最有力的前瞻性证据。 此外，我还开发了一项有关PD（帕金森基因和环境研究（PAGE））的新研究项目，以研究NIH-AARP饮食和健康研究中PD的环境和遗传危险因素，这是一个大型的前瞻性队列，该研究由NCI研究的Arthur Schatzkin博士在NCI研究中于1990年代中期启动。超过50岁或50岁以上的美国男女参加了1995年和1996年的基线调查，现在正在进行一项随访调查，以记录包括PD在内的慢性疾病的发生。因此，该队列为PD研究提供了出色的基础设施。 页面研究包括两个阶段：第1页是一项纵向研究，旨在研究饮食/生活方式是否与PD风险有关，使用在基线上收集的暴露信息和后续行动中确定的PD病例。第2页将是一项病例对照研究，旨在检查与PD相关的其他环境/职业风险因素，并需要从两个病例和选定的控制措施中进一步回顾性暴露数据收集。对于这两个项目，关键是对PD病例进行准确的诊断确认，并且两个项目的内在组成部分是DNA收集，这将使我们能够对Diet-Gene / Environment-Gene相互作用进行病例对照分析。因此，将作为第1页的一部分进行PD诊断确认和DNA收集。在第2页中，我们将使用计算机辅助电话采访（CATI）进行回顾性数据收集。特别令人感兴趣的是对农药，重金属，药物和传染病史的暴露。 最终，我们预计将根据其他具有相似设计的大型前瞻性队列的年龄和性别特定的发病率确认大约1,000例PD病例（1996-2004）。这将使这项研究成为迄今为止PD的最大纵向研究，因此对我们对晚期发作零星PD的环境和遗传原因的理解做出了重大贡献。 我们启动了今年的页面I项目的数据收集，并计划在明年晚些时候完成。在同一时间，我们计划启动II页项目。 除了这些项目外，我还在开展一些有关PD和相关神经退行性条件的较小项目。